Redd1 protects against post‑infarction cardiac dysfunction by targeting apoptosis and autophagy

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Cellular Signaling

Background:

• Post-infarction cardiac remodeling involves mammalian target of rapamycin (mTOR) signaling.
• Regulated in development and DNA damage response-1 (Redd1) influences DNA repair and mTOR activity.
• The specific role of Redd1 in cardiac function post-myocardial infarction (MI) remains largely unexplored.

Purpose of the Study:

• To investigate the role of Redd1 in the chronic phase of heart failure following MI.
• To elucidate the underlying mechanisms of Redd1's action in the context of MI.
• To determine if Redd1 overexpression offers cardioprotective effects post-MI.

Main Methods:

• Utilized a mouse model of myocardial infarction (MI).
• Employed adeno-associated virus 9 (AAV9) for cardiomyocyte-specific Redd1 overexpression.
• Assessed left ventricular function, cardiac remodeling, apoptosis, autophagy, and mTOR signaling pathway activation.

Main Results:

• Redd1 expression was downregulated in the mouse heart post-MI.
• Redd1 overexpression improved left ventricular dysfunction and reduced cardiac expansion.
• Redd1 overexpression suppressed myocardial apoptosis, enhanced autophagy, and inhibited mTOR pathway phosphorylation.

Conclusions:

• Redd1 overexpression demonstrates a protective effect against heart failure development and persistence after MI.
• The cardioprotective mechanisms involve reduced apoptosis and enhanced autophagy via the mTOR signaling pathway.
• Redd1 represents a potential therapeutic target for managing heart failure post-MI.